Detection of tumor DNA at the margins of colorectal cancer liver metastasis

Matthias Holdhoff, Kerstin Schmidt, Frank Diehl, Nishant Aggrawal, Philipp Angenendt, Katharine Romans, Daniel L. Edelstein, Michael Torbenson, Kenneth W. Kinzler, Bert Vogelstein, Michael A. Choti, Luis A. Diaz

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. Experimental Design: We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12, and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Results: Mutations were identified in each patient's resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in 5 of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA and of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Conclusions: Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases.

Original languageEnglish (US)
Pages (from-to)3551-3557
Number of pages7
JournalClinical Cancer Research
Volume17
Issue number11
DOIs
StatePublished - Jun 1 2011

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Liver Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
DNA
Neoplasms
Liver
Biopsy
Drug Therapy
Mutation
Hepatectomy
Colonic Neoplasms
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Holdhoff, M., Schmidt, K., Diehl, F., Aggrawal, N., Angenendt, P., Romans, K., ... Diaz, L. A. (2011). Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clinical Cancer Research, 17(11), 3551-3557. https://doi.org/10.1158/1078-0432.CCR-10-3087

Detection of tumor DNA at the margins of colorectal cancer liver metastasis. / Holdhoff, Matthias; Schmidt, Kerstin; Diehl, Frank; Aggrawal, Nishant; Angenendt, Philipp; Romans, Katharine; Edelstein, Daniel L.; Torbenson, Michael; Kinzler, Kenneth W.; Vogelstein, Bert; Choti, Michael A.; Diaz, Luis A.

In: Clinical Cancer Research, Vol. 17, No. 11, 01.06.2011, p. 3551-3557.

Research output: Contribution to journalArticle

Holdhoff, M, Schmidt, K, Diehl, F, Aggrawal, N, Angenendt, P, Romans, K, Edelstein, DL, Torbenson, M, Kinzler, KW, Vogelstein, B, Choti, MA & Diaz, LA 2011, 'Detection of tumor DNA at the margins of colorectal cancer liver metastasis', Clinical Cancer Research, vol. 17, no. 11, pp. 3551-3557. https://doi.org/10.1158/1078-0432.CCR-10-3087
Holdhoff M, Schmidt K, Diehl F, Aggrawal N, Angenendt P, Romans K et al. Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clinical Cancer Research. 2011 Jun 1;17(11):3551-3557. https://doi.org/10.1158/1078-0432.CCR-10-3087
Holdhoff, Matthias ; Schmidt, Kerstin ; Diehl, Frank ; Aggrawal, Nishant ; Angenendt, Philipp ; Romans, Katharine ; Edelstein, Daniel L. ; Torbenson, Michael ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Choti, Michael A. ; Diaz, Luis A. / Detection of tumor DNA at the margins of colorectal cancer liver metastasis. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 11. pp. 3551-3557.
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